TNF/iNOS-producing dendritic cells mediate innate immune defense against bacterial infection

Immunity. 2003 Jul;19(1):59-70. doi: 10.1016/s1074-7613(03)00171-7.


Dendritic cells (DCs) present microbial antigens to T cells and provide inflammatory signals that modulate T cell differentiation. While the role of DCs in adaptive immunity is well established, their involvement in innate immune defenses is less well defined. We have identified a TNF/iNOS-producing (Tip)-DC subset in spleens of Listeria monocytogenes-infected mice that is absent from CCR2-deficient mice. The absence of Tip-DCs results in profound TNF and iNOS deficiencies and an inability to clear primary bacterial infection. CD8 and CD4 T cell responses to L. monocytogenes antigens are preserved in CCR2-deficient mice, indicating that Tip-DCs are not essential for T cell priming. Tip-DCs, as the predominant source of TNF and iNOS during L. monocytogenes infection, orchestrate and mediate innate immune defense against this intracellular bacterial pathogen.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / analysis
  • CD11b Antigen / analysis
  • CD11c Antigen / analysis
  • Dendritic Cells / immunology*
  • Immunity, Innate*
  • Listeria monocytogenes
  • Listeriosis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Receptors, CCR2
  • Receptors, Chemokine / physiology
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Antigens, Differentiation
  • CD11b Antigen
  • CD11c Antigen
  • Ccr2 protein, mouse
  • Receptors, CCR2
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • monocyte-macrophage differentiation antigen
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse